A new look on Alzheimer’s and Parkinson’s disease: in vivo imaging of neurodegenerative disease processes in the retina

Abstract

Purpose : Accumulating evidence suggests that, rather than trying to access information about the disease state of the CNS in the brain, one could exploit the unique properties of the eye. In vivo assessments of retinal structure, electrophysiological function, and performance of vision-driven tasks, have revealed specific signs of deterioration in Alzheimer’s (AD) and Parkinson’s disease (PD) patients and animal models. In this study, we exploit the advantages of the retina as a model organ for CNS research, and put forward two objectives: (i) characterization of mouse models for the study of AD/PD in the retina; and (ii) development of an integrated workflow for in vivo examination of retinal neurodegeneration, inflammation, vascular changes, and protein aggregation.

Methods : Several AD/PD mouse models were examined, including an AAV vector-mediated alpha-synuclein (aSYN) overexpression model and multiple transgenic AD and PD mouse lines. Longitudinal, non-invasive follow-up of disease progression in the retina was performed, by in vivo imaging with optical coherence tomography (OCT), confocal laser scanning ophthalmoscopy (cSLO) and vision-guided behavior tests (including visual acuity and contrast sensitivity). These assays were complemented with biomolecuar techniques and (immuno)histological stainings for relevant disease processes and specific retinal cell markers.

Results : Different retinal manifestations and diverging time courses of disease were detected in the AD/PD mouse models under study. Overall, our results indicate that (i) cSLO can be used to study cell death, inflammation, vasculature and protein aggregation at single-cell resolution; (ii) retinal neurodegeneration can be quantified via OCT; and (iii) these disease manifestations can be correlated to functional deficits.

Conclusions : By combining AD/PD models with a workflow for longitudinal in vivo follow-up of disease - comprising of methods and end points that can be readily transferred to the clinic - we can provide valuable research tools (i) to gather new insights into the disease mechanisms of AD/PD, (ii) to perform preclinical drug development, and (iii) to reduce the number of animals needed for AD/PD research.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.